Familial Hypercholesterolemia Biomarker Distribution in Dried Blood Spots.

OBJECTIVE: To evaluate distribution profiles of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (apoB) as candidate markers of familial hypercholesterolemia in newborns, taking into consideration potential confounding factors, such as gestational age, birth weight, sex, and race. STUDY DESIGN: TC, LDL-C, and apoB were measured from 10 000 residual deidentified newborn dried blood spot cards. Concentrations for each biomarker were reported as multiples of the median, with emphasis on describing the 99th percentile values based on birth weight, gestational age, sex, and race. Seasonal variation of biomarkers was also explored. RESULTS: LDL-C and apoB had distribution curves with tails showing extreme elevation, whereas the distribution of TC was less elevated and had the smallest range. Neonates born at early gestational age and low birth weight had significantly greater 99th percentile of multiples of the median values for apoB but not TC or LDL-C. Differences in biomarker concentration based on sex and race were minimal. All biomarkers showed greatest concentrations in the winter as compared with summer months. CONCLUSIONS: LDL-C and apoB had distribution curves supporting candidacy for neonatal familial hypercholesterolemia screening. Future studies are needed to correlate newborn screening results with molecular testing to validate these 2 biomarkers, along with measured cholesterol levels later in childhood.

Turner syndrome may be associated with hepatic adenoma.

Turner syndrome, caused by complete or partial loss of an X chromosome, is marked by a range of clinical manifestations including short stature, cardiovascular and renal disease. Hepatic involvement is an increasingly recognized concern. Steatosis and elevated transaminases are commonly observed in this population, but case reports have also described hepatic adenoma. Hepatic adenomas are rare, occurring in one per million people in the general population. They are typically benign but malignant transformation or rupture can occur. We sought to investigate whether Turner syndrome is associated with hepatic adenoma. Patients with Turner syndrome encountered at a single, academic institution between 2006 and 2020 were identified using ICD-10 codes and demographic, medication, laboratory, and imaging data were analyzed. Of the 228 patients identified, 46.9% had liver function testing, which were abnormal in 48.6%. Five of 77 patients with hepatic imaging had abnormalities. Three patients (1.3%) had hepatic adenoma, one after presenting in hemorrhagic shock due to rupture. These findings suggest that patients with Turner syndrome may have an increased risk for developing hepatic adenoma. Annual monitoring of liver function tests is already recommended in Turner syndrome. The addition of periodic hepatic imaging may also be beneficial.

Cascade screening for familial hypercholesterolemia from pediatric index cases diagnosed through universal screening.

Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant disorder causing elevated low density lipoprotein cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease. Universal cholesterol screening in childhood leads to children serving as the index case for their family, but efficacy of cascade screening and genetic counseling in this population is not well understood. The institutional pediatric lipid clinic database was queried from 2011 to 2022 for subjects <18 years who met clinical HeFH diagnostic criteria (N = 256). Median peak LDL-C was 198 mg/dL (interquartile range 179-238 mg/dL) and 69.5 % of subjects were the index case. The number of new HeFH cases identified per index case was 3.55 ± 1.87. Genetic counseling was offered to 38.7 % of subjects and genetic testing was completed by 10.9 %, 53.6 % of whom had a pathogenic or likely pathogenic genetic variant for HeFH. Our findings highlight the effectiveness of cascade screening from pediatric index cases identified through universal screening. However, genetic counseling and genetic testing may be underutilized in this population.

The impact of insurance on equitable access to non-invasive prenatal screening (NIPT): private insurance may not pay.

Non-invasive prenatal testing (NIPT), is a prenatal screening test for chromosomal aneuploidies (trisomy 21, trisomy 18, and trisomy 13). While women under 35 years of age with no other risk factors are considered low risk for pregnancies with aneuploidy, most babies with aneuploidy are born to low-risk women. Across the USA, including Wisconsin, many private insurances do not cover initial NIPT for low-risk women, creating a potential financial burden that may limit patient selection of NIPT. Low-risk women with public insurance in Wisconsin are covered for NIPT. This pilot study determined if a difference exists in NIPT uptake based on insurance type in low-risk pregnant women in their first trimester. It also explored genetic counselor perspectives on how insurance coverage for NIPT is addressed with patients. Women with public insurance were 3.43 times more likely to have NIPT as an initial screen for aneuploidy than women with private insurance, indicating that insurance coverage may present a barrier to care. Additionally, analysis showed no evidence of different demographic variables interacting with another to impact outcome after allowing for insurance coverage (X214 = 14.301, p = 0.428). Our data also suggests that more genetic counselors would recommend NIPT to patients if insurance coverage was not a barrier and were more likely to discuss financial risks associated with NIPT when a patient had private insurance. We conclude that some women cannot choose one of the safest and most sensitive prenatal aneuploidy screening tests due to financial barriers put into place by the lack of insurance coverage.